DJ-1 mutations are a very rare cause of recessive parkinsonism, accounting for a handful of cases worldwide. The protein involved has been shown by several laboratories to be involved in oxidative stress responses although the precise molecular function is unknown. At a cellular level, one of the effects of a loss of DJ-1 is that mitochondrial function is compromised. This may be related to oxidative stress, as mitchondria are a major source of reactive oxygen species (ROS), although this is uncertain. In prior years, we have identified some of the key residues in the DJ-1 protein that are important for cellular function, particularly cysteine 106 which becomes modified after exposure to ROS and glutamate 18, which stabilizes the modified C106 residue. To try and develop our ideas about DJ-1 further, we have been exploring two aspects of its function. First, we have started to characterize the effects of DJ-1 deficiency on mitochondrial function. We find that a lack of DJ-1 causes loss of mitochondrial membrane potential and an increase in markers of autophagy, the process by which defective mitochondria are removed from the cell. Second, we have developed novel mutations that identify functionally critical sites on DJ-1 for protection against mitochondrial damage.